Open AccessHigh levels of thyroid hormones promote recurrence of Graves' disease via overexpression of B‐cell‐activating factor
Author(s) -
Liu Shu,
Miao JingJing,
Zhou Xiao,
Sun Qi,
Mao XiaoMing
Publication year - 2022
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.24701
Subject(s) - graves' disease , trab , b cell activating factor , thyroid , medicine , endocrinology , triiodothyronine , hormone , flow cytometry , immunology , b cell , antibody
Background Elevated thyroid hormone (TH) levels have been suggested to be associated with the pathological progression of Graves' disease (GD). However, direct evidence from clinical studies remains unclear. Methods Peripheral blood samples were collected from patients with or without the recurrence of Graves' hyperthyroidism (GH) and healthy donors. Thyroid tissue samples were obtained from patients with benign thyroid nodules. To assess the differentiation of autoreactive B cells, the expression of B‐cell‐activating factor (BAFF) and the proportion of CD11c+/–IgG+/− subsets of B cells stimulated by high levels of triiodothyronine (T3) in vivo and in vitro were examined by ELISA, flow cytometry, western blotting, and qRT‐PCR. Results Serum BAFF levels in patients with GD were significantly and positively correlated with FT3, FT4, and TRAb levels. Furthermore, the ratio of abnormally differentiated CD11c+ autoreactive B cells positively correlated with BAFF and TRAb. High levels of triiodothyronine (T3) induced BAFF overexpression in thyroid follicular cells and mononuclear cells of the normal thyroid in vitro, thereby promoting the differentiation of CD11c+IgG+ autoreactive secretory B cells (ASCs). However, the precise knockdown of BAFF expression significantly inhibited the abnormal differentiation of ASCs. Conclusion The pathological progression of GD was prolonged and exacerbated by autoimmune positive feedback modulation caused by high TH levels. BAFF could be considered a potential target for localized thyroid immunosuppressive treatment of Graves' hyperthyroidism recurrence.